JCI - Diabetic and ER-stressed pancreatic islet β cells are in need of some JNK removal

jci.org

Skeletal Muscle PGC‐1α Remodels Mitochondrial Phospholipidome but Does Not Alter Energy Efficiency for ATP Synthesis

Background The coupling of oxygen consumption to ATP synthesis via oxidative phosphorylation (OXPHOS) is central for cellular energy homeostasis. Some studies suggest exercise training increases the.....

onlinelibrary.wiley.com

Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α | Nature Cardiovascular Research

Endurance exercise promotes adaptive growth and improved function of myocytes, which is supported by increased mitochondrial activity. In skeletal muscle, these benefits are in part transcriptionally coordinated by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). The importance of PGC-1α to exercise-induced adaptations in the heart has been unclear. Here we show that deleting PGC-1α specifically in cardiomyocytes prevents the expected benefits from exercise training and instead leads to heart failure after just 6 weeks of training. Consistent with this, in humans, rare genetic variants in PPARGC1A, which encodes PGC-1α, are associated with increased risk of heart failure. In this model, we identify growth differentiation factor 15 (GDF15) as a key heart-secreted mediator that contributes to this dysfunction. Blocking cardiac Gdf15 expression improves cardiac performance and exercise capacity in these mice. Finally, in human heart tissue, lower cardiomyocyt

doi.org

Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α - Nature Cardiovascular Research

Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

nature.com

Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α - Nature Cardiovascular Research

Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

nature.com

Sex difference in BAT thermogenesis depends on PGC-1α–mediated phospholipid synthesis in mice - Nature Communications

Brown adipose tissue (BAT) plays a role in energy expenditure but its thermogenic activities differ between sexes. Here, the authors show that PGC-1α enhances mitochondrial function and BAT thermogene...

nature.com

Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia - Nature Cancer

Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during c...

nature.com

Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia - Nature Cancer

Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during c...

nature.com

RBM43 controls PGC1α translation and a PGC1α-STING signaling axis

Dumesic et al. identify RBM43 as an RNA-binding protein that governs mitochondrial biogenesis through suppression of PGC1α translation. RBM43 is induced by inflammatory signaling and controls a diabetogenic regulatory axis in adipocytes whereby decreased…

dlvr.it

SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO - Nature

Analysis of large-scale CRISPR screening data, combined with experiments in patient-derived tumour organoid models, identifies PELO as a potential therapeutic target in chromosomal 9p21.3-deleted canc...

nature.com

SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO - Nature

Analysis of large-scale CRISPR screening data, combined with experiments in patient-derived tumour organoid models, identifies PELO as a potential therapeutic target in chromosomal 9p21.3-deleted canc...

nature.com

Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity - Nature Cell Biology

Latorre-Muro et al. show that the cytosolic chaperone PPID drives insertion of the mitochondrial import receptor TOM70 into the mitochondrial outer membrane, thereby regulating body temperature, gluco...

nature.com

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity - Nature Cancer

Puigserver and colleagues show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of ...

nature.com

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity - Nature Cancer

Puigserver and colleagues show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of ...

nature.com

nature.com

Fine-tuning tumor immunogenicity with mitochondrial complex I - Nature Cancer

Targeting mitochondrial metabolic activity is an active area of cancer research. A study now finds that a selective deficiency in mitochondrial complex I in melanoma cells increases mitochondrial acet...

nature.com

Time-resolved mitochondrial-focused screening identifies regulatory components of oxidative metabolism

Defects in mitochondrial oxidative metabolism contribute to various genetic inherited disorders, termed mitochondrial diseases, with limited treatment options. Given the lack of functional annotation ...

biorxiv.org

Structural basis of respiratory complex adaptation to cold temperatures

High-resolution structures of respiratory I:III2 complexes from brown fat adapted to cold temperatures reveal a distinct supercomplex assembly with rotated CIII2 that displays higher electron transfer and catalytic efficiency, which has implications for increased respiration in response to physiological energy-demanding conditions.

cell.com